Collagens are a family of nineteen different fibrous structural proteins that are found in several types of tissues. Collagens are the most abundant proteins in mammals, and are essential for the formation of connective tissue such as skin, bone, tendon, cartilage, blood vessels and teeth. Members of the collagen family can be distinguished from one another by the degree of cross-linking between collagen fibers and by the amount of carbohydrate units (e.g., galactose or glucosylgalactose) attached to the collagen fibers. Hydroxylated lysine residues (hydroxylysine) are essential for stability of cross-linking and as attachment points for carbohydrate units.
The enzyme lysyl hydroxylase catalyzes the hydroxylation of lysine residues to form hydroxylysine. Lysyl hydroxylase targets the lysine residue of the sequence X-lys-gly. Two isoforms of lysyl hydroxylase have been characterized, termed PLOD (procollagen-lysine, 2-oxoglutarate 5-dioxygenase) and PLOD2. The two enzymes share 75% sequence homology, with even higher similarity in the C-terminal region (Valtavaara, M. et al. (1997) J. Biol. Chem. 272: 6831-4).
Diminished lysyl hydroxylase activity is involved in certain connective tissue disorders. In particular mutations, including a truncation and duplications within the coding region of the gene for PLOD, have been described in patients with type VI Ehlers-Danos syndrome (Hyland, J. et al. (1992) Nature Genet. 2: 228-31; Hautala, T. et al. (1993) Genomics 15: 399-404).
The discovery of a new human lysyl hydroxylase-like protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, treatment, and prevention of cancer and connective tissue disorders.